SCAN:Zalpha-domains: at the intersection between RNA editing and innate immunity

ITQB Scan Seminar

Title: Zalpha-domains: at the intersection between RNA editing and innate immunity

Speaker: Alekos Athanasiadis

Affiliation: Researcher at Protein – Nucleic Acids Interactions Group (IGC)

Abstract:

Zalpha-domains: at the intersection between RNA editing and innate immunity

    Since the first crystal structure of DNA in 1979 we know that DNA can dynamically adopt alternative conformations to the classical right-handed B-DNA helix proposed by Watson and Crick. The left-handed helical conformation known as Z-DNA, adopted by purine/pyrimidine repeats, has since been very extensively studied in vitro but if it actually has a role in biological systems has remained obscure until the mid-90s. This changed in 1995 with the discovery in Alexander’s Rich lab that a domain of the RNA editing enzyme ADAR1 specifically binds to Z-DNA and it was followed by the crystal structure of the first Z-DNA/protein complex few years later.

    Since the initial discovery of the ADAR1 Z-DNA binding domain several proteins have been found to have the same type of nucleic-acids binding domain forming a domain family called Zalpha. Biochemical and structural studies reveal how the binding of these domains extends to dsRNA allowing for Zalpha domains to interact with both RNA and DNA of the same sequence.
 
    Interestingly all proteins having a Zalpha-domain are either components of the antiviral interferon response or viral proteins involved in shutting down the exact same pathway. The ability of Zalpha to domains to interact with negatively supercoiled CG repeats appears to be linked to the surveillance apparatus that detects foreign nucleic acids in the cytoplasm.

Moreover these domains can be used to study the Z-DNA conformation per se by providing a means for its stabilization at relevant physiological conditions and how such studies have revealed the mechanism through which Z-DNA formation in genomic sequences is linked to the known genomic instability induced by CpG repeats.
 
As part of our interest in understanding the role of A to I RNA editing in animals and the ADAR1 editing enzyme, we have been studying the Zalpha domain family and in my talk I will present our work and discuss our current understanding of the protein/nucleic acids interactions involved in the recognition of Z-DNA.